Background and purpose: The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
Experimental approach: Psoriasis-like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL-23. Praziquantel was either orally or topically administered during the psoriasis induction period.
Key results: Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T-cells. Praziquantel also decreased STAT3 phosphorylation in HEK-A/F cells. Down-regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
Conclusion and implications: These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
Keywords: IL-23; STAT3; Th17 cell; imiquimod; praziquantel; psoriasis.
© 2021 The British Pharmacological Society.